This aim of this Phase I SBIR proposal from Applikate Technology, LLC, is to validate the use of ClearView, a novel approach to performing complete and non-destructive imaging of tissue specimens, for primary pathology of lung biopsies. Error rates for diagnoses of lung cancer from biopsies may run as high as 15%. Although the root causes of errors are diverse, immunohistochemistry (IHC) and molecular analysis are some of the newest and most valuable tools employed for surgical pathology accuracy. Indeed, results from IHC and molecular analysis are now considered critical for determining the path of care and the appropriate agent for chemotherapy. However, their use is dependent on having enough sample tissue after initial morphologic evaluation. Applikate Technologies has developed ClearView, a proprietary approach for morphologic evaluation of biopsies without worry that tissue will be exhausted before IHC and molecular analysis studies. In addition, ClearView enables complete, non-destructive imaging of entire biopsy samples, improving limits of slide-based histology that include partial tissue visualization, artifacts of preparation, non-quantitative interpretation, limited growth pattern information, and extensive manual preparation. The specific aims of the proposal are to: 1) Demonstrate primary lung cancer diagnosis on samples processed with ClearView; 2) Verify the compatibility of ClearView processing with IHC and molecular analyses and 3) Develop software for automated pseudo-coloring and image normalization in order to present the pathologist with images that reliably mimic conventional staining with hematoxylin and eosin. Successful completion of these aims will set the stage for a Phase II proposal to develop a system ready for commercial deployment. Phase III will establish a specialized lung pathology service based on ClearView.